1. MYCOBACTERIUM ABSCESSUS

2. Mycobacterium abscessus
Rapid growing mycobacterium
Environmental contaminant
Formerly part of “M. chelonae-complex” till 1992
Subspecies of M. abscessus
M. abscessus senso strictu
M. massiliense
M. bolletii

3. Mycobacterium abscessus
Pulmonary disease most common
Cutaneous disease
Disseminated disease rare (mostly immunosuppressed w/ corticosteroids)
Bacteremia/ endocarditis: described in hemodialysis patients

4. Clusters of M. abscessus infection after cosmetic Rx or injection of alternative medicine
Year
Place
Type of Rx received
Outcome US
Injection of adrenal cortex extract
Cutaneous infection
2001
Seoul, South Korea
Acupuncture
2002
New York, US
Intramammary injection of silicone
Dominican Republic
Abdominoplasty
2012
Hong Kong
CIK therapy
Septicemia

5. Mycobacterium abscessus
Most pathogenic and chemotherapy-resistant rapid-growing mycobacterium
Intrinsic resistance
Low permeability of cell wall
Drug export systems
Antibiotic-modifying/ inactivating enzymes
Genetic polymorphism of targeted gene
Acquired resistance
Macrolide resistance
Aminoglycoside resistance

6. Intrinsic resistance Low permeability of cell wall Drug export systems
High lipid content (up to 60% of dry weight)
Drug export systems
Mycobacterial membrane protein large (MmpL) transporter family
ABC-type multidrug transporter family

7. Intrinsic resistance Antibiotic-modifying/ inactivating enzymes
Rifampicin ADP-ribosyltransferase and mono-oxygenase → rifampicin resistance
Aminoglycoside 2-N-acetyltransferase and phosphotransferases → aminoglycosiade resistance
Genetic polymorphism of target genes
Mutations in embB → ethambutol resistance
Mutations in quinolone resistance-determining regions (QRDRs) → fluoroquinolones resistance

8. Acquired resistance Macrolide resistance
Macrolide → inhibit ribosomal translocation
Inducible ribosomal methylase erm(41) gene → modify ribosome binding site
Clarithromycin induces erm(41) to a significantly greater extent than azithromycin
??azithromycin preferred over clarithromycin

9. Acquired resistance Aminoglycoside resistance
Aminoglycoside → interfere proof-reading process, causing errors in synthesis with premature termination
Mutations affecting 16S rRNA

10. Treatment strategy Limited, extra-pulmonary disease
Clarithromycin alone (Acquired mutational resistance not observed when treating localized infections with macrolide monotherapy)
Amikacin +/- cefoxitin/ imipenem may be added for two weeks until clinical improvement in more severe cases
Duration guided by clinical response: typically 4 months. Osteomyelitis: 6 month minimum recommended
Infected foreign bodies should be removed

11. Treatment strategy Pulmonary or severe extrapulmonary disease
In vitro data not yielded effective regimen for treating pulmonary disease
May not achieve sputum culture negativity even with 12 months of therapy
Lung disease should be considered a chronic, incurable infection

12. Treatment strategy Pulmonary or severe extrapulmonary disease
Combination therapy always recommended:
Clarithromycin 500mg PO BD plus Amikacin IV (15mg/kg/d) plus either cefoxitin IV (2gm Q4H) or Imipenem IV (1gm Q6H)
Duration: combination therapy w/ injectable agents + clarithromycin at least 2-4 months but duration often limited by adverse effects
Maintenance: once with good effect with combination therapy, consider switch to oral clarithromycin OR azithromycin indefinitely ("suppressive treatment")

13. Treatment strategy Pulmonary or severe extrapulmonary disease
Other agents: little good data to guide on selection or use in combination
Tigecycline 100mg IV load then 50mg IV Q12H
Little reported clinical data but may be in vitro susceptible and could be substituted as one of the injectables. Often poorly tolerated due to GI distress

14. Treatment strategy Pulmonary or severe extrapulmonary disease
Linezolid 600mg Q12H PO
potentially useful oral agent in pts in whom parental Rx not tolerated or feasible
Clofazimine
may have in vitro activity, little clinical experience

15. Mycobacterium abscessus
Most pathogenic and chemotherapy-resistant rapid growing mycobacterium
Most commonly caused pulmonary disease
Clusters of cutaneous disease after cosmetic injections reported
Disseminated disease/ bacteremia is rare
?related to severe DIC, but no case report identified